Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling.
Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR)-induced immunological synapse (IS) formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of alpha beta T cells, together with defects in cell activation and cytokine production following TCR triggering. The mutant T cells further displayed excessive accumulation yet reduced dynamics of F-actin and the WASP-Arp2/3 machinery at the IS, correlating with extended cell-cell contact. Cell signaling was also affected with the basal activation of the stress kinases sAPK/JNK1/2; and deficits in TCR-induced Ca2+ influx and phosphorylation and degradation of the inhibitor of NF-kappaB (I kappa B). Coronin-1A therefore links cytoskeleton plasticity with the functioning of discrete TCR signaling components. This function may be required to adjust TCR responses to selecting ligands accounting in part for the homeostasis defect that impacts alpha beta T cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages.
Mugnier
Bénédicte
B
Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, Marseille, France.
Nal
Béatrice
B
Verthuy
Christophe
C
Boyer
Claude
C
Lam
David
D
Chasson
Lionel
L
Nieoullon
Vincent
V
Chazal
Geneviève
G
Guo
Xiao-Jun
XJ
He
Hai-Tao
HT
Rueff-Juy
Dominique
D
Alcover
Andrés
A
Ferrier
Pierre
P
D000199:Actins; D000818:Animals; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D003599:Cytoskeleton / Q000378:metabolism*; D006706:Homeostasis; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*
D000199:Actins; D016207:Cytokines; D008840:Microfilament Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C072061:coronin proteins